It is planned to continue to study human renal transplant recipients (25 per year) by in vitro immunological methods, to continue to collect and catalogue blocking antibodies developing in these recipients using the sensitive discriminatory MLC (D MLC) and to continue to build on a panel of blocking antisera with the eventual prospect of LD typing (not necessarily MHC) for specific clinical therapeutic use of these antisera. In experimental animals, it is planned to proceed with canine studies using low MLR responders for the development of enhancement of second set renal allografts when the D MLC and serial immunological monitoring indicates the presence of pure blocking antibody serveral months after first set renal transplantation. Animals which are both immunosuppressed and untreated will be studied and organ perfusion with blocking antibody will be performed. The obvious significance of this work is the eventual use of this type of agent as a specific immunosuppressant in clinical trials. It is also planned to determine the biologic feasibility of the use of several agents and modalities which could modulate graft antigenicity. This will involve three specific objectives: 1. Development of a canine model in which emphasis is placed on whole organ perfusion and the study of responsible mechanism and variables associated with prolongation of graft survival by plant lectins and blocking antibody. 2. Development of a mouse skin graft model. Emphasis will be placed on immunogenetic factors and treatment of donor skin and lymphocytes with lectins and other agents in tissue culture. 3. Development of an in vitro system for quantitating changes in graft immunogenicity by pre-treatment with Con A. In our clinical renal transplant recipients as well as in animals it is proposed to continue with prospective lymphocyte in vitro monitoring as we now perform it using a battery of tests including the MLR, T and B cell assays, PHA response, antibody mediated cellular immune lysis tests and killer cell assays as well as to develop more sensitive in vitro measures of immune reactivity.